Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast
Source abstract
Abstract
Magnetic resonance imaging contrast agents are currently designed by modifying their structural and physiochemical properties to improve relaxivity and to enhance image contrast. Here, we show a general method for increasing relaxivity by confining contrast agents inside the nanoporous structure of silicon particles. Magnevist, gadofullerenes and gadonanotubes were loaded inside the pores of quasi-hemispherical and discoidal particles. For all combinations of nanoconstructs, a boost in longitudinal proton relaxivity r(1) was observed: Magnevist, r(1) ≈ 14 mM(-1) s(-1)/Gd(3+) ion (∼ 8.15 × 10(+7) mM(-1) s(-1)/construct); gadofullerenes, r(1) ≈ 200 mM(-1) s(-1)/Gd(3+) ion (∼ 7 × 10(+9) mM(-1) s(-1)/construct); gadonanotubes, r(1) ≈ 150 mM(-1) s(-1)/Gd(3+) ion (∼ 2 × 10(+9) mM(-1) s(-1)/construct). These relaxivity values are about 4 to 50 times larger than those of clinically available gadolinium-based agents (∼ 4 mM(-1) s(-1)/Gd(3+) ion). The enhancement in contrast is attributed to the geometrical confinement of the agents, which influences the paramagnetic behaviour of the Gd(3+) ions. Thus, nanoscale confinement offers a new and general strategy for enhancing the contrast of gadolinium-based contrast agents.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Lanthanide and Transition Metal Complexes · Magnetism in coordination complexes · Advanced NMR Techniques and Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (36)
Show source-provided references
1. Mansfield, P. Snapshot magnetic resonance imaging. Angew. Chem. Int. Ed. 43, 5456–5464 (2004).10.1002/anie.200460078 ↗
2. Caravan, P., Ellison, J. J., McMurry, T. J. & Lauffer, R. B. Gadolinium(III) chelates as MRI contrast agents: structure, dynamics and applications. Chem. Rev. 99, 2293–2352 (1999).10.1021/cr980440x ↗
3. Lauffer, R. B. Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chem. Rev. 87, 901–927 (1987).10.1021/cr00081a003 ↗
4. Merbach, A. E. & Toth, E. The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging (John Wiley & Sons, 2001).
5. A market summary report for MRI is available at http://www.imvinfo.com/
6. Laurent, S., Vander Elst, L. & Muller, R. N. Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents. Contrast Media Mol. Imaging 1, 128–137 (2006).10.1002/cmmi.100 ↗
7. Toth, E., Helm, L. & Merbach, A. E. Relaxivity of gadolinium(III) complexes: theory and mechanism, in The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging 45–119 (John Wiley & Sons, 2001).
8. Tasciotti, E. et al. Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nature Nanotech. 3, 151–157 (2008).10.1038/nnano.2008.34 ↗
9. Toth, E. et al. Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents. J. Am. Chem. Soc. 127, 799–805 (2005).10.1021/ja044688h ↗
10. Sayes, C. M. et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 4, 1881–1887 (2004).10.1021/nl0489586 ↗
11. Sitharaman, B. et al. Superparamagnetic gadonanotubes are high-performance MRI contrast agents. Chem. Commun. 31, 3915–3917 (2005).10.1039/b504435a ↗
12. Hartman, K. B. et al. Gadonanotubes as ultrasensitive pH-smart probes for magnetic resonance imaging. Nano Lett. 8, 415–419 (2008).10.1021/nl0720408 ↗
13. Ashcroft, J. M. et al. Functionalization of individual ultra-short single-walled carbon nanotubes. Nanotechnology 17, 5033–5037 (2006).10.1088/0957-4484/17/20/001 ↗
14. Chiappini, C. et al. Tailored porous silicon microparticles: fabrication and properties. Chem. Phys. Chem. 11, 1029–1035 (2010).10.1002/cphc.200900914 ↗
15. Li, Z. & Drazer, G. Fluid enhancement of particle transport in nanochannels. Phys. Fluids 18, 117102–117108 (2006).10.1063/1.2372715 ↗
16. Mulder, W. J. M. et al. Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging. Acc. Chem. Res. 42, 904–914 (2009).10.1021/ar800223c ↗
17. Strijkers, G. J. et al. Relaxivity of liposomal paramagnetic MRI contrast agents. Magn. Reson. Mater. Phys., Biol. Med. 18, 186–192 (2005).10.1007/s10334-005-0111-y ↗
18. Talanov, V. S. et al. Dendrimer-based nanoprobe for dual modality magnetic resonance and fluorescence imaging. Nano Lett. 6, 1459–1463 (2006).10.1021/nl060765q ↗
19. Avedano, S. et al. Maximizing the relaxivity of HSA-bound gadolinium complexes by simultaneous optimization of rotation and water exchange. Chem. Commun. 45, 4726–4728 (2007).10.1039/b714438e ↗
20. Yang, J. J. et al. Rational design of protein-based MRI contrast agents. J. Am. Chem. Soc. 130, 9260–9267 (2008).10.1021/ja800736h ↗
21. Richard, C. et al. Noncovalent functionalization of carbon nanotubes with amphiphilic Gd3+ chelates: toward powerful T1 and T2 MRI contrast agents. Nano Lett. 8, 232–236 (2008).10.1021/nl072509z ↗
22. Laus, S. et al. Understanding paramagnetic relaxation phenomena for water-soluble gadofullerenes. J. Phys. Chem. C 111, 5633–5639 (2007).10.1021/jp070458o ↗
23. Laus, S. et al. Destroying gadofullerene aggregates by salt addition in aqueous solution of Gd@C60(OH)x and Gd@C60[C(COOH2)]. J. Am. Chem. Soc. 127, 9368–9369 (2005).10.1021/ja052388+ ↗
24. Kruk, D. & Kowalewski, J. General treatment of paramagnetic relaxation enhancement associated with translational diffusion. J. Chem. Phys. 130, 174104–174112 (2009).10.1063/1.3119635 ↗
25. Botta, M. Second coordination sphere water molecules and relaxivity of gadolinium(III) complexes: implications for MRI contrast agents. Eur. J. Inorg. Chem. 2000, 399–407 (2000).10.1002/(SICI)1099-0682(200003)2000:3<399::AID-EJIC399>3.0.CO;2-B ↗
26. Lebduskova, P. et al. Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer: an 17O and 1H relaxation study of its Gd(III) complex. Dalton Trans. 28, 3399–3406 (2006).10.1039/B517847A ↗
27. Decuzzi, P. & Ferrari, M. The adhesive strength of non-spherical particles mediated by specific interactions. Biomaterials 27, 5307–5314 (2006).10.1016/j.biomaterials.2006.05.024 ↗
28. Decuzzi, P., Pasqualini, R., Arap, W. & Ferrari, M. Intravascular delivery of particulate systems: does geometry really matter? Pharm. Res. 26, 235–243 (2009).10.1007/s11095-008-9697-x ↗
29. Decuzzi, P. et al. Size and shape effects in the biodistribution of intravascularly injected particles. J. Control. Release 141, 320–327 (2009).10.1016/j.jconrel.2009.10.014 ↗
30. Godin, B. et al. Multistage mesoporous silicon-based nanocarriers: biocompatibility and controlled degradation in physiological fluids. CRS Newsletter 25, 9–11 (2008).
31. Nunn, A. D., Linder, K. E. & Tweedle, M. F. Can receptors be imaged with MRI agents? Q. J. Nucl. Med. 41, 155–162 (1997).
32. Tanaka, T. et al. Sustained small interfering RNA delivery by mesoporous silicon particles. Cancer Res. 70, 3687–3696 (2010).10.1158/0008-5472.CAN-09-3931 ↗
33. Anglin, E. J., Cheng, L., Freeman, W. R. & Sailor, M. J. Porous silicon in drug delivery devices and materials. Adv. Drug Deliv. Rev. 60, 1266–1277 (2008).10.1016/j.addr.2008.03.017 ↗
34. Park, J. H. et al. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nature Mater. 8, 331–336 (2009).10.1038/nmat2398 ↗
35. Slowing, I. I., Vivero-Escoto, J. L., Wu, C. W. & Lin, V. S. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv. Drug Deliv., Rev. 60, 1278–1288 (2008).10.1016/j.addr.2008.03.012 ↗
36. Gu, Z., Peng, H., Hauge, R. H., Smalley, R. E. & Margrave, J. L. Cutting single-wall carbon nanotubes through fluorination. Nano Lett. 2, 1009–1013 (2002).10.1021/nl025675+ ↗